Electron beam sculpting of tunneling junction for nanopore DNA sequencing

ABSTRACT

A technique for a nanodevice is provided that includes a reservoir filled with a conductive fluid and a membrane separating the reservoir. The membrane includes an electrode layer having a tunneling junction formed therein. A nanopore is formed through the membrane, and the nanopore is formed through other layers of the membrane such that the nanopore is aligned with the tunneling junction of the electrode layer. When a voltage is applied to the electrode layer, a tunneling current is generated by a base in the tunneling junction to be measured as a signature for distinguishing the base. When an organic coating is formed on an inside surface of the tunneling junction, transient bonds are formed between the electrode layer and the base.

CROSS-REFERENCE TO RELATED APPLICATIONS AND PRIORITY CLAIM

This application is a continuation of U.S. Non-Provisional applicationSer. No. 13/359,729, entitled “ELECTRON BEAM SCULPTING OF TUNNELINGJUNCTION FOR NANOPORE DNA SEQUENCING”, filed Jan. 27, 2012, which isbased on and claims priority to U.S. Provisional Patent Application61/437,102, entitled “ELECTRON BEAM SCULPTING OF TUNNELING JUNCTION FORNANOPORE DNA SEQUENCING”, filed Jan. 28, 2011, both of which areincorporated herein by reference in their entirety.

BACKGROUND

Exemplary embodiments relate to nanodevices, and more specifically to atunneling junction and nanopore structure in a nanodevice

Nanopore sequencing is a method for determining the order in whichnucleotides occur on a strand of Deoxyribonucleic acid (DNA). A nanoporeis a small hole on the order of several nanometers in internal diameter.The theory behind nanopore sequencing has to do with what occurs whenthe nanopore is immersed in a conducting fluid and an electric potential(voltage) is applied across the nanopore. Under these conditions, aslight electric current due to conduction of ions through the nanoporecan be measured, and the amount of current is very sensitive to the sizeand shape of the nanopore. If single bases or strands of DNA pass (orpart of the DNA molecule passes) through the nanopore, this can create achange in the magnitude of the current through the nanopore. Otherelectrical or optical sensors can also be put around the nanopore sothat DNA bases can be differentiated while the DNA passes through thenanopore.

DNA could be driven through the nanopore by using various methods. Forexample, an electric field might attract the DNA towards the nanopore,and it might eventually pass through it. The scale of the nanopore meansthat the DNA may be forced through the hole as a long string, one baseat a time, rather like thread through the eye of a needle.

BRIEF SUMMARY

According to an exemplary embodiment, a method of configuring ananodevice is provided. The method includes filing a reservoir with aconductive fluid, configuring a membrane to separate the reservoir inthe nanodevice, where the membrane includes an electrode layer having atunneling junction formed therein. The method includes configuring themembrane to have a nanopore formed through other layers of the membranesuch that the nanopore is aligned with the tunneling junction of theelectrode layer. When a voltage is applied to the electrode layer, atunneling current is generated by a base in the tunneling junction to bemeasured as a current signature for distinguishing the base. When anorganic coating is formed on an inside surface of the tunnelingjunction, transient bonds are formed between the electrode layer and thebase.

Other systems, methods, apparatus, design structures, and/or computerprogram products according to embodiments will be or become apparent toone with skill in the art upon review of the following drawings anddetailed description. It is intended that all such additional systems,methods, apparatus, design structures, and/or computer program productsbe included within this description, be within the scope of theexemplary embodiments, and be protected by the accompanying claims. Fora better understanding of the features, refer to the description and tothe drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The subject matter which is regarded as the invention is particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The forgoing and other features are apparent from thefollowing detailed description taken in conjunction with theaccompanying drawings in which:

FIG. 1A illustrates a schematic of a process to make a tunnelingjunction by focused electron beam cutting and to fine tune the junctionsize by expanded electron beam in accordance with an exemplaryembodiment.

FIG. 1B illustrates a schematic continuing a process to make a tunnelingjunction in accordance with an exemplary embodiment.

FIG. 1C illustrates a schematic continuing a process to make a tunnelingjunction in accordance with an exemplary embodiment.

FIG. 2A illustrates a schematic of the integration of a tunnelingjunction with a nanopore in accordance with an exemplary embodiment.

FIG. 2B illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 2C illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 2D illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 2E illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 2F illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 3A illustrates a schematic of a tunneling junction nanopore devicefor DNA sequencing in accordance with an exemplary embodiment.

FIG. 3B illustrates a schematic of a tunneling junction nanopore devicefor DNA sequencing with an organic coating in accordance with anexemplary embodiment.

FIG. 4A illustrates a schematic of the integration of a tunnelingjunction with a nanopore in accordance with an exemplary embodiment.

FIG. 4B illustrates a schematic continuing integration of a tunnelingjunction with a nanopore in accordance with an exemplary embodiment.

FIG. 4C illustrates a schematic continuing the integration of atunneling junction with a nanopore in accordance with an exemplaryembodiment.

FIG. 5 illustrates examples of molecules for self-assembly insidenanopores in accordance with an exemplary embodiment.

FIG. 6 illustrates a computer utilized according to exemplaryembodiments.

FIG. 7 illustrates a flow chart according to an exemplary embodiment.

DETAILED DESCRIPTION

Exemplary embodiments provide an approach to make a nanometer sizetunneling junction by focus electron beam cutting, and then to fine tunethe junction size, by expanded electron beam techniques. Exemplaryembodiments also include the integration of such tunneling junction witha nanopore for the purpose of DNA sequencing in a nanodevice.

Recently, there has been growing interest in applying nanopores assensors for rapid analysis of biomolecules such as DNA, ribonucleic acid(RNA), protein, etc. Special emphasis has been given to applications ofnanopores for DNA sequencing, as this technology is believed to hold thepromise to reduce the cost of sequencing below $1000/human genome. Oneissue in nanopore DNA sequencing is electrically differencing individualDNA bases by leveraging this nanopore platform.

In accordance with exemplary embodiments, an approach is disclosed whichuses a focused electron beam (e.g., utilizing a beam size as small as0.4 nm) to cut a thin metal layer (shown as cut line 105 in FIG. 1A) toform the tunneling junction. Under a low intensity electron beam,material migration can occur, and the material migration can be used tofine tune the gap size of the tunneling junction. If the thin metallayer is on a free-standing membrane, one can also make the nanopore(shown as nanopore 206, 208 in FIGS. 2B-2I) through the top of themembrane at the gap to create the tunneling junction right at theentrance, at the inner surface, and/or the exit of the nanopore for DNAsequencing purposes via the tunneling current.

Now turning to the figures, FIGS. 1A-1C illustrate a schematic of aprocess to make a tunneling junction by focused electron beam cuttingand to fine tune the junction size by expanded electron beam accordingto an exemplary embodiment. FIGS. 1A-1C are top views of the schematic.In FIG. 1A, a substrate 101 can be any electrically insulatingsubstrate, and layer 102 can be any electrically conductive layer suchas a metal on top of the substrate 101. Voltage is applied by voltagesource 103 between two ends of the conductive layer 102 and current ismonitored through the ammeter 104. A focused electron beam (not shown)could be as small as 0.4 nm, and the focused electron beam performs linescanning shown as line 105 at the center location of conductive layer102 (e.g., in a vacuum). One skilled in the art understands electronbeam lithography (e-beam lithography), and understands the practice ofscanning a beam of electrons in a patterned fashion across a surface.

The high energy, high density electron beam can sputter/etch material onits way into the vacuum gradually. When the voltage at voltage source103 is being applied, the current measured by its corresponding ammeter104 serves as a feedback that the current through ammeter 104 will dropdown to zero (0) once the conductive layer 102 is cut into two halves bythe electron beam, as shown in FIG. 1B. FIG. 1B shows a left half andright half of the conductive layer 102. In this way, one can create atunneling junction 106 without damaging the underneath substrate 101.The tunneling junction 106 which is a nanosize gap between twoelectrically conductive parts corresponds to the line 105 previouslyshown in FIG. 1A.

In FIG. 1B, with an expanded (i.e., low intensity) electron beamcovering area 107, the (metal) material in the conductive layer 102 canmigrate and the gap size of the tunneling junction 106 can be tuned;that is the tunneling junction 106 can be reduced or increased in sizeto be the tunneling junction 108 shown in FIG. 1C.

For example, to achieve the desired size tunneling junction (gap) 108, alow intensity electron beam can be used to bombard the conductive layer102 at the tunneling junction (gap) 108 (106 in FIG. 1B); this willcause the conductive layer 102 material to get softer and flow undersurface tension. The low intensity electron beam can be utilized tocause the conductive layer 102 material to flow such that the tunnelingjunction (gap) 108 is widened and/or flow such that the tunnelingjunction (gap) 108 is narrowed. As seen by the decrease in size of thetunneling junction (gap) 106 in FIG. 1B to the tunneling junction (gap)108 in FIG. 1C (which is not drawn to scale), material migration hascaused the tunneling junction (gap) 106 to narrow. If the substrate 101is a thin membrane, the whole tuning process can be monitored under atransmission electron microscope in real-time. Thus, one can acquire(tune) the exact size of the tunneling junction (gap) 108 by turning offthe electron beam at the right moment. After fine tuning the tunnelingjunction 106, the tunneling junction 106 is now represented as thefinely tuned tunneling junction (gap) 108 in FIG. 1C.

FIGS. 2A-2F illustrate a schematic of the integration of the tunnelingjunction 108 with a nanopore in accordance with an exemplary embodiment.FIGS. 2A, 2B, 2D, and 2E (including 4A and 4B) are a cross-sectionalview of the schematic, and FIGS. 2C and 2F (including 4C) are top viewsof the schematic. In FIG. 2A, the substrate 201 can be any substrate,such as Si (silicon). Layers 202 and 203 are electrically insulatingfilms, such as Si₃N₄ (compound of silicon and nitrogen). The insulatinglayer 203 serves as an etching mask for etching thorough the substrate201 via either dry or wet etching, and the etching stops on insulatinglayer 202. In this way, part of the insulating layer 202 will be afree-standing membrane. Conductive layer 204 (corresponding toconductive layer 102 in FIG. 1) is an electrically conductive layer, andtunneling junction 205 (corresponding to tunneling junction/gap 108 inFIG. 1) is the tunneling junction made in the free-standing membranepart of conductive layer 204 using the method described in FIG. 1. Thetunneling junction 205 will be visible under a transmission electronmicroscope, and a nanometer size pore (nanopore) 206 can be made throughthe tunneling junction 205 and the underneath insulating layer 202, asshown in FIG. 2B. In this way, the tunneling junction 205 is integratedwith the nanopore 206. As seen in FIG. 2B, the nanopore 206 is a holethrough the insulating layer 202 while the tunneling junction 205 is agap in the conductive layer (metal) 204.

FIG. 2C shows a top view of the schematic in FIG. 2B. As seen in the topview of FIG. 2C, the tunneling junction 205 (corresponding to tunnelingjunction/gap 108 in FIG. 1) is only between the conductive layer (metal)204 (corresponding to conductive layer 102), and the tunneling junction205 splits the conductive layer 204 into a left half and a right half.The nanopore 206 is formed through the tunneling junction 205 and goesthrough the substrate 201.

In order to work with an electrically conductive solution, an insulating(cap) layer 207 (also called the passivation layer which may be a layerof oxide and/or silicon nitride) is deposited on the conductive layer204, as shown in FIG. 2D (e.g., right after the tunneling junction 205is made). The tunneling junction 205 will be visible under atransmission electron microscope and a nanometer size pore (nanopore)208 can be made through the tunneling junction 205 and the underneathinsulating layer 202, as shown in FIG. 2E. In this way, the tunnelingjunction 205 is embedded in the nanopore 208. The nanopore 206 may nowbe considered part of the nanopore 208. Via windows 209 and 210 areopened through the insulating layer 207 down to the conductive layer204, for electrically accessing the two sides of the tunneling junction205. The windows 209 and 210 will be used as electrodes/connections forconnecting, e.g., a wire to the left and right halves of the conductivelayer 204.

FIG. 2F illustrates the top view of FIG. 2E. In FIG. 2F, the conductivelayer 204 (shown as an outline with a dotted line) is buried underneaththe insulation (passivation) layer 207 with windows 209 and 210 of theconductive layer 204 exposed. Although not visible in FIG. 2F, thenanopore 208 goes through the insulating layer 202 and the insulation(passivation) layer 207.

FIGS. 4A, 4B, and 4C illustrate a variation of FIGS. 2A-2F in which thenanopore 208 and tunneling junction are made in the same electron beamcutting process and have the same shape in accordance with an exemplaryembodiment. An insulating (cap) layer 207 (also called the passivationlayer which may be a layer of oxide and/or silicon nitride) is depositedon the conductive layer 204, as shown in FIG. 4A. A focused electronbeam is used to cut through all layers 207, 204, and 202 at thefreestanding membrane part and to cut conductive layer 204 into twohalves, as shown in FIG. 4B. In this way, the tunneling junction 205 andthe nanopore 208 have exactly the same shape. Via windows 209 and 210are opened through the insulating layer 207 down to the conductive layer204, for electrically accessing the two sides of the tunneling junction205. The windows 209 and 210 will be used as electrodes/connections forconnecting, e.g., a wire to the left and right halves of the conductivelayer 204.

FIG. 4C illustrates the top view of FIG. 4B. In FIG. 4C, the conductivelayer 204 (shown as a dotted line) is buried underneath the insulating(passivation) layer 207 with windows 209 and 210 of the conductive layer204 exposed. Although not visible in FIG. 4C, the nanopore 208 goesthrough the insulating layer 202 and the insulating (passivation) layer207.

FIGS. 3A and 3B illustrate a schematic (system) of a tunneling junction(e.g., tunneling junction 106, 108, and 205) and nanopore device 300 forDNA sequencing according to an exemplary embodiment. FIGS. 3A and 3Bshow a cross-sectional view of the tunneling junction and nanoporedevice 300.

In FIGS. 3A and 3B, elements 301-310 are the same as elements 201-210respectively. However, FIG. 3B includes an organic coating as discussedherein. The tunneling junction and nanopore device 300 partitions tworeservoirs 311 and 312. Electrically conductive solution 313 fills thetwo reservoirs 311 and 312 as well as the nanopore 308. A negativelycharged DNA 314 (with each base illustrated as base 315) can be driveninto the nanopore 308 by a voltage of the voltage source 318 appliedbetween the two reservoirs 311 and 312 via two electrodes 316 and 317,respectively. Voltage of the voltage source 319 is applied between thetwo sides (at left window 309 and right window 310) of the tunnelingjunction 305, and a baseline tunneling current is monitored at ammeter320. The baseline tunneling current may be stored in memory 15 of acomputer 600 (shown in FIG. 6) for further use as discussed herein. AsDNA bases 315 pass through the tunneling junction 305 (which is the gapin the conductive (metal) layer 304), each of the DNA bases 315 can beindentified by its respective tunneling current signal at the ammeter320.

For example, voltage source 318 is turned on to drive the DNA 314 intothe tunneling junction 305 which is the gap separating the conductivelayer 304 into two halves. When, e.g., a base 315 a is in the tunnelingjunction 305, voltage source 319 is turned on (while voltage source 318is turned off) to measure the tunneling current of the base 315 a. Forinstance, with voltage applied by voltage source 319, current flowsthrough window 309 (acting as an electrode) of conductive layer 304,through the conductive layer 304, into the conductive solution (liquid)313, into the DNA base 315 a (which produces the tunneling currentsignature), out through the conductive solution 313, into the right sideof the conductive layer 304, out through the window 310 (acting as anelectrode), and into the ammeter 320 for measurement. The ammeter 320may be implemented by and/or integrated in the computer 600 (testequipment) for measuring the baseline tunneling current and tunnelingcurrent generated by the DNA base 315 a. A software application 605 ofthe computer 600 is configured to measure, display, plot/graph, analyze,and/or record the measured tunneling current for each DNA base 315 thatis tested. In the example above, the software application 605 (and/or auser utilizing the software application 605) can compare the baselinetunneling current measured with no DNA base 315 in the tunnelingjunction 305 to the tunneling current corresponding to each DNA base 315(at a time) that is measured in tunneling junction 305. In the example,the tunneling current (signal) for the DNA base 315 a is comparedagainst the baseline tunneling current by the software application 605(or a user utilizing the software application 605). The tunnelingcurrent (signature) for the DNA base 315 a may have particularcharacteristics that are different from the baseline tunneling currentmeasured by the ammeter 320, and the tunneling current (signatures) forthe DNA base 315 a can be utilized to identify and/or differentiate theDNA base 315 a from other DNA bases 315 on the DNA 314.

For example, the measured tunneling current signature for DNA base 315 amay have a positive pulse, a negative pulse, a higher or lower current(magnitude), an inverse relationship, a rising or falling plot, aparticular frequency, and/or any other difference from the baselinetunneling current that can be determined by the software application 605(and/or a user viewing the display 45 of the two different plots). Thisunique tunneling current signature can be utilized (by the softwareapplication 605) to distinguish the DNA base 315 a from other DNA bases315. Note that, the tunneling current measured at ammeter 320 betweenelectrode layers does not require any electrical wiring between the leftand right parts (which will be shown as electrodes 304 a and 304 b inFIG. 3B) of the conductive (electrode) layers 304 as electrons simplymove from one electrode to the other in a quantum mechanical way. Forexample, there will be a baseline tunneling current when DNA base 315 ais away (e.g., with distance much longer than the wavelength of anelectron) from the tunneling junction 305. When DNA base 315 a is close(e.g., within the distance of the wavelength of an electron) to thetunneling junction 305, the tunneling path of the electron will bererouted to tunnel from the left part of the conductive (electrode)layer 304 to the DNA base 315 a and then to the right part of theconductive (electrode) layer 304. In this way, the tunneling current(electrons) through the DNA base 315 a will create a current signature(such as an increase of tunneling current, typically in the order oftens of pA (picoamperes)) added onto the baseline tunneling currenttrace. The tunneling current across DNA bases is dependent on theelectronic and chemical structure of the DNA bases; thus, a differentDNA base will generate a different tunneling current signature. If thedifference between the tunneling current signatures of different basesis small or stochastic, repeating measurements on the same DNA base canbe done; a histogram of the amplitudes of the tunneling currentsignatures can be fit and the statistical data will provide enoughresolution to differentiate DNA bases.

FIG. 3B utilizes the approach discussed for FIG. 3A except that theconductive layer 304 is coated with organic coating 325 a and 325 b,which can form transient bonds 321 a and 321 b (such as a hydrogen bond(i.e., transient bonds 321) with the DNA base 315). In FIG. 3B, thesetransient bonds 321 formed by the organic coating 325 a and 325 b willfix the orientation of the DNA base 315 and the relative distance of theDNA base 315 to the conductive layer 304, for improving the tunnelingcurrent signal measured by ammeter 320 and for better identifying DNAbases 315. If the organic coating 325 a and 325 b and/or transient bonds321 a and 321 b are electrically conductive, they will help to shrinkthe tunneling gap size and enhance the tunneling current signatures too.Also, the transient bonds 321 a and 321 b by the organic coating 325 aand 325 b hold the DNA 314 in place against thermal motion whenmeasuring the tunneling current of the base 315. The forces of thermalmotion may cause the DNA 314 to move, but the transient bonds 321 a and321 b fix the base 315 in the tunneling junction 305 against the DNAmovement caused by thermal motion.

In one implementation, the organic coating 325 a and 325 b consists ofbifunctional small molecules which at one end form covalent bonds withconductive layer 304, and at the other end (of the organic coating 325a/b) which is exposed in the nanopore 308, the organic coating 325 a and325 b consists of functionalities which can form strong hydrogen bondswith DNA and/or can protonate nucleotides to form acid baseinteractions. If the conductive layer 304 is made of metals such asgold, palladium, platinum etc., the first functionality which bonds tothe conductive layer 304 can be chosen as thiols, isocyanides, and/ordiazonium salts. If the conductive layer 304 is made of titaniumnitrides or indium tin oxide (ITO), the covalent bonding functionalityis chosen from phosphonic acid, hydroxamic acid, and/or resorcinolfunctionality. The small bifunctional molecules are designed in such away that any charge formation due to interaction with DNA can easily betransferred to the conductive layer 304 and therefore a pi-conjugatedmoiety (e.g., benzene, diphenyl, etc.) are sandwiched between twofunctionalities. The second functionality is a group which can form astrong hydrogen bond with DNA. Examples of such groups include but arenot limited to alcohols, carboxylic acids, carboxamides, sulfonamides,and/or sulfonic acids. Other groups which can be used to forminteractions with DNA are individual self-assembled nucleotides. Forexample, adenine monophosphonic acid, guanine monophosphonic acid, etc.,can be self-assembled on titanium nitride electrodes or mercapto thymineor mercapto cytosine self-assembles on metal electrodes such as goldand/or platinum. FIG. 5 illustrates examples of molecules forself-assembly inside nanopores according to exemplary embodiments. Themolecules may be utilized as the organic coating 325 a and 325 b.

Referring to FIG. 3B, as discussed above, the voltage source 318 isapplied to move the DNA 314 into the nanopore 308. When voltage of thevoltage source 319 is applied (and the voltage source 318 is turnedoff), current flows through left electrode 304 a, into the organiccoating 325 a, into the transient bond 321 a (which acts as or can bethought of as a wire), into the DNA base 315 a (producing the tunnelingcurrent), out through the transient bond 321 b, out through the organiccoating 325 b, out through the right electrode 304 b, and into theammeter 320 to measure the tunneling current of the DNA base 315 a. Theammeter 320 may be integrated with the computer 600, and the computer600 can display on display 45 the tunneling current of the DNA base 315a versus the baseline tunneling current measured when no base 315 is inthe tunneling junction 305.

FIG. 7 illustrates a method 700 according to exemplary embodiments, andreference can be made to FIGS. 1, 2, and 3.

At operation 705, a tunneling junction 108, 205, 305 is made by electronbeam sculpting (cutting or size-tuning). Using a low intensity electronbeam, the tunneling junction 108, 205, 305 can be widened by causing thematerial (metal) of the conductive layer 102, 204, 304 to migrate awayfrom the tunneling junction gap, thus making the gap wider; similarly,using a low intensity electron beam spread across area 107 in FIG. 1,the tunneling junction 108, 205, 305 can be narrowed to cause thematerial of the conductive layer 102, 204, 304 to flow toward (into) thetunneling junction gap thus make the gap smaller.

At operation 710, the tunneling junction 108, 205 is integrated with ananopore 208 as shown in FIGS. 2B-2F. The integrated (combined)tunneling junction 205 and nanopore 208 form a hole through multiplelayers 207, 204, and 202 as shown in FIG. 2E. The distinction betweenthe tunneling junction 205 and the nanopore 208 can be seen in FIG. 2F.This distinction is carried through to the tunneling junction 305 shownin FIG. 3 in which the tunneling junction 305 is the gap between theconductive layer 304 (i.e., separating the conductive layer 304 into twohalves) but not layers 307, 302, 301, and 303. In one implementation,the tunneling junction 108, 205 is formed prior to forming the nanopore208 (and/or nanopore 206).

At operation 715, the nanopore 208 partitions two conductive ionicbuffer reservoirs 312 and 313, and the DNA 314 is electrically loadedinto the nanopore 308 and the tunneling junction 305. The tunnelingjunction 305 is between the left half 304 a and right half 304 b of theconductive layer 304. The left and right halves 304 a and 304 b serve aselectrodes for accessing the tunneling junction 305 (and the base 315therein) by the voltage source 319 to measure the tunneling current withammeter 320.

At operation 720, the DNA bases 315 are differentiated using thetunneling current of each individual base 315 (measured by ammeter 320)with and/or without organic coating 325 a and 325 b on the insidesurface of the tunneling junction 305. The computer 600 can measure,analyze, differentiate, display, and record/store (in memory 15) thedifferent tunneling currents measured for the different bases 315 of theDNA 314. The tunneling current measurements of the bases 315 with theorganic coating 325 a and 325 b causing the transient bonds 321 a and321 b would be different from the tunneling currents measurements of thesame bases 315 without the organic coating 325 a and 325 b and withoutthe transient bonds. For example, the tunneling current measured forbase 315 a with the organic coating 325 a and 325 b (causing transientbonds 321 a and 321 b) may have a greater magnitude than without theorganic coating 325 a and 325 b.

Now turning to FIG. 6, FIG. 6 illustrates a block diagram of thecomputer 600 having various software and hardware elements forimplementing exemplary embodiments. The computer 600 may be utilized inconjunction with any elements discussed herein.

The diagram depicts the computer 600 which may be any type of computingdevice and/or test equipment (including ammeters, voltage sources,connectors, etc.). The computer 600 may include and/or be coupled tomemory 15, a communication interface 40, display 45, user interfaces 50,processors 60, and software 605. The communication interface 40comprises hardware and software for communicating over a network andconnecting (via cables, plugs, wires, electrodes, etc.) to thenanodevices discussed herein. Also, the communication interface 40comprises hardware and software for communicating with, operativelyconnecting to, reading, and controlling voltage sources, ammeters,tunneling currents, etc., as discussed herein. The user interfaces 50may include, e.g., a track ball, mouse, pointing device, keyboard, touchscreen, etc, for interacting with the computer 600, such as inputtinginformation, making selections, independently controlling differentvoltages sources, and/or displaying, viewing and recording tunnelingcurrent signatures for each base, etc.

The computer 600 includes memory 15 which may be a computer readablestorage medium. One or more applications such as the softwareapplication 605 (e.g., a software tool) may reside on or be coupled tothe memory 15, and the software application 605 comprises logic andsoftware components to operate and function in accordance with exemplaryembodiments in the form of computer executable instructions. Thesoftware application 605 may include a graphical user interface (GUI)which the user can view and interact with according to exemplaryembodiments.

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.) or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, aspects of the present invention may take the form of acomputer program product embodied in one or more computer readablemedium(s) having computer readable program code embodied thereon.

Any combination of one or more computer readable medium(s) may beutilized. The computer readable medium may be a computer readable signalmedium or a computer readable storage medium. A computer readablestorage medium may be, for example, but not limited to, an electronic,magnetic, optical, electromagnetic, infrared, or semiconductor system,apparatus, or device, or any suitable combination of the foregoing. Morespecific examples (a non-exhaustive list) of the computer readablestorage medium would include the following: an electrical connectionhaving one or more wires, a portable computer diskette, a hard disk, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,a portable compact disc read-only memory (CD-ROM), an optical storagedevice, a magnetic storage device, or any suitable combination of theforegoing. In the context of this document, a computer readable storagemedium may be any tangible medium that can contain, or store a programfor use by or in connection with an instruction execution system,apparatus, or device.

A computer readable signal medium may include a propagated data signalwith computer readable program code embodied therein, for example, inbaseband or as part of a carrier wave. Such a propagated signal may takeany of a variety of forms, including, but not limited to,electro-magnetic, optical, or any suitable combination thereof. Acomputer readable signal medium may be any computer readable medium thatis not a computer readable storage medium and that can communicate,propagate, or transport a program for use by or in connection with aninstruction execution system, apparatus, or device.

Program code embodied on a computer readable medium may be transmittedusing any appropriate medium, including but not limited to wireless,wireline, optical fiber cable, RF, etc., or any suitable combination ofthe foregoing.

Computer program code for carrying out operations for aspects of thepresent invention may be written in any combination of one or moreprogramming languages, including an object oriented programming languagesuch as Java, Smalltalk, C++ or the like and conventional proceduralprogramming languages, such as the “C” programming language or similarprogramming languages. The program code may execute entirely on theuser's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on a remotecomputer or entirely on the remote computer or server. In the latterscenario, the remote computer may be connected to the user's computerthrough any type of network, including a local area network (LAN) or awide area network (WAN), or the connection may be made to an externalcomputer (for example, through the Internet using an Internet ServiceProvider).

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer program instructions. These computer program instructions maybe provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, element components,and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated

The flow diagrams depicted herein are just one example. There may bemany variations to this diagram or the steps (or operations) describedtherein without departing from the spirit of the invention. Forinstance, the steps may be performed in a differing order or steps maybe added, deleted or modified. All of these variations are considered apart of the claimed invention.

While the exemplary embodiments of the invention have been described, itwill be understood that those skilled in the art, both now and in thefuture, may make various improvements and enhancements which fall withinthe scope of the claims which follow. These claims should be construedto maintain the proper protection for the invention first described.

What is claimed is:
 1. A method of configuring a nanodevice, the methodcomprising: filing a reservoir with a conductive fluid; configuring amembrane to separate the reservoir in the nanodevice, the membranecomprising an electrode layer having a tunneling junction formedtherein; and configuring the membrane to have a nanopore formed throughother layers of the membrane such that the nanopore is aligned with thetunneling junction of the electrode layer; wherein when a voltage isapplied to the electrode layer, a tunneling current is generated by abase in the tunneling junction to be measured as a current signature fordistinguishing the base; wherein when an organic coating is formed on aninside surface of the tunneling junction, transient bonds are formedbetween the electrode layer and the base; and wherein the organiccoating includes a selection from hydroxamic acid, resorcinolfunctionality, adnine monophosphonic acid, guanine monophosphonic acid,sulfonamides, and sulfonic acid.
 2. The method of claim 1, wherein thetunneling junction is cut into the electrode layer by a focused electronbeam.
 3. The method of claim 1, wherein a first insulating layer isunderneath a substrate and a second insulating layer is above thesubstrate; and wherein the electrode layer having the tunneling junctionis above the second insulating layer.
 4. The method of claim 3, whereina third insulating layer is above the electrode layer; and wherein thesecond insulating layer and the third insulating layer are the otherlayers through which the nanopore is formed.
 5. The method of claim 4,wherein the nanopore formed through the second insulating layer and thethird insulating layer is aligned to the tunneling junction in theelectrode layer.
 6. The method of claim 1, wherein the transient bondshold the base in place against thermal motion.
 7. The method of claim 1,wherein the transient bonds improve the current signature of the base.